Is it Non-Hodgkin's lymphoma or tubercular lymphadenitis: A diagnostic dilemma? Aashita, Yadav V, Sharma R, Kapoor A, Thakur P,

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CASE REPORT

Ahead of print publication

Is it Non-Hodgkin's lymphoma or tubercular lymphadenitis: A diagnostic dilemma?

Aashita¹, Vikas Yadav¹, Rajiv Sharma¹, Anuja Kapoor¹, Pragyat Thakur²
¹ Department of Radiation Oncology, VMMC and Safdarjung Hospital, New Delhi, India
² Department of Radiation Oncology, Homi Bhabha Cancer Hospital, Sangrur, Punjab (Affiliated to HBNI, Mumbai, Maharashtra), India

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Date of Submission	18-Mar-2022
Date of Decision	22-Mar-2022
Date of Acceptance	22-Apr-2022
Date of Web Publication	27-Oct-2022

Abstract

The incidence of non-Hodgkin's lymphoma (NHL) is increasing, more so in tuberculosis (TB) endemic low and middle-income countries. Both of them have overlapping presentation that makes it difficult to differentiate them clinically. Here, we describe a case of 60-year-old male with oropharyngeal NHL with cervical and axillary lymphadenopathy. After completion of chemotherapy, there was complete resolution of oropharyngeal mass, but lymph nodes (LN) had responded partially. At this point, he was diagnosed with pulmonary TB and was started on antitubercular treatment (ATT). The residual LN resolved completely with the ATT. The patient is currently disease free. The case reported here highlights the dilemma in diagnosing a LN to be tubercular or lymphomatous.

Keywords: Coexistence, non-Hodgkin's lymphoma, tubercular lymphadenitis

How to cite this URL:
Aashita, Yadav V, Sharma R, Kapoor A, Thakur P. Is it Non-Hodgkin's lymphoma or tubercular lymphadenitis: A diagnostic dilemma?. J Appl Sci Clin Pract [Epub ahead of print] [cited 2023 Mar 27]. Available from: http://www.jascp.org/preprintarticle.asp?id=358984

Introduction

Non-Hodgkin's lymphoma (NHL) is a disorder with neoplastic transformation of lymphocytes.^[1] Currently, NHL is the eleventh most common cancer by both incidence and death in India.^[2],[3] On the other hand, tuberculosis (TB) is a chronic inflammatory disease with a quarter of global cases reported from India.^[4] As both NHL and TB can have similar clinical presentation, patients are misdiagnosed. Here, we report a case of oropharyngeal NHL with a diagnostic uncertainty of lymph nodes (LN) being tubercular or lymphomatous.

Case Report

A 60-year-old male presented with epistaxis and bleeding from the mouth with progressive painless swelling in the right side of the neck and axilla for 6 months without history of fever, drenching night sweats, or weight loss. The patient tested negative for human immunodeficiency virus, hepatitis B surface antigen, and antibodies against hepatitis C virus. Contrast-enhanced computed tomography (CECT) revealed an oropharyngeal mass with multiple discrete cervical and axillary LN [Table 1] and [Figure 1].

Table 1: Comparison of radiological findings of patient at the time of diagnosis, completion of chemotherapy, and completion of antitubercular treatment

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Figure 1: CECT images showing A-at time of diagnosis. (A1) oropharyngeal mass, (A2) enlarged cervical LN, (A3) enlarged axillary LN, (A4) normal imaging of chest. B-after completion of chemotherapy. (B1) complete response of oropharyngeal mass, (B2) residual cervical LN, (B3) residual axillary LN, (B4) pericardial and pleural effusion. C-After completion of 6 months of ATT. (C1) section of whole body with no evidence of disease, (C2) resolved pericardial and pleural effusion. CECT: Contrast enhanced computed tomography, LN: Lymph node, ATT: Antitubercular treatment

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Histopathological evaluation of the oropharyngeal mass revealed undifferentiated tumor [Figure 2] that was positive for cytokeratin, epithelial membrane antigen, neuron-specific enolase, leukocyte common antigen, and CD20 but negative for HMB45 and myogenin. Serum lactate dehydrogenase was 449U/L with normal hemogram and liver function and renal function tests. Bone marrow biopsy revealed immature precursor cells in scattered and interstitial pattern that were positive for BCL2 and CD20. Positron emission tomography CT (PET-CT) was not done due to financial constraints. The patient received six cycles of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. Response assessment CECT, after three cycles of chemotherapy, showed complete response in oropharyngeal mass but partial response in level IV and V cervical and axillary nodes. However, multiple bilateral nodules appeared in both the lungs with moderate pleural and pericardial effusion [Table 1] and [Figure 1]. Acid-fast bacilli were not seen in the sputum, but Mycobacterium TB (M. tb) was detected in cartridge-based nucleic acid amplification test with rifampicin sensitivity. Treatment for pulmonary TB (PTB) was started as we were doubtful for residual nodes to be tubercular. After 2 months of antitubercular treatment (ATT), the patient had no palpable cervical or axillary node. The patient took ATT for 6 months after which PET-CT was done.

Figure 2: HPE of biopsy from oropharyngeal mass showing undifferentiated tumour that was cytokeratin, EMA, NSE, LCA, CD20 positive but negative for HMB45 and myogenin indicating NHL. HPE: Histopathological evaluation, EMA: Epithelial membrane antigen, NSE: Neuron specific enolase, LCA: Leukocyte common antigen, NHL: Non-Hodgkin's Lymphoma

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The patient responded well to ATT as the residual nodes along with bilateral lung nodules, pleural and pericardial effusion resolved completely. After completion of ATT, there was no evidence of any disease on PET-CT. Currently, the patient is disease free and on follow-up for 3 years.

Discussion

NHL patients usually present with painless progressively enlarging LN with or without systemic symptoms including fever, night sweats, weight loss, pruritus, and fatigue. However, as lymphoma can also originate at extranodal sites, patients can present with diverse symptoms depending on area involved.^[1]

TB is endemic in low and middle income countries like India. Tubercular lymphadenitis (TBLN) is the most common form of extra-PTB seen in approximately 40% of cases. TBLN usually is a nontender chronic enlarged LN, which is firm, discrete, or matted presenting infrequently with fever and bilateral involvement.^[5]

As clinical presentation of both NHL and TBLN is overlapping with painless enlarged LN with or without conventional symptoms, it is difficult to differentiate between them clinically and are commonly misdiagnosed.^[6] Immunosuppressed states have been correlated with incidence of both NHL and TB. In fact, there is 1.8 times higher chance to develop NHL in a patient with prior history of TB.^[7] Patients can also present with simultaneous TB and lymphoma mimicking or hiding each other, resulting in a missed diagnosis of either. Literature review shows possibility of coexistence of TB with lymphoma where both can be mistaken for each other and diagnosis remains elusive. Fifteen cases (who had no history of any prior immunocompromised state) have been reported till now with coexisting NHL and TB [Table 2]. Pathological and microbiological confirmation is required to aid in better differentiation and exact treatment.

Table 2: Cases reported till now with co-existence of non-Hodgkin's lymphoma and tuberculosis (with no history of any prior immunocompromised state)

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The case reported here was an oropharyngeal NHL with cervical and axillary lymphadenopathy. The patient had a partial response on first-line chemotherapy, but as sputum was positive for M. tb, the patient was started on ATT due to coexisting TB and suspicion of residual cervical and axillary node to be TBLN following which he had an excellent. Hence, it was decided to complete ATT course with discontinuation of further chemotherapy till obvious node enlargement or disease relapses. The patient responded completely with ATT.

Pondering upon the unusual course of management in this patient who had a partial response in nodes with standard chemotherapy followed by complete resolution with ATT, the following hypothesis with possible explanations can be considered:

It might be that initial LN involvement was tubercular in nature: The initial decrease in size of LN could be ascertained to doxorubicin which has antibacterial activity as it inhibits DNA replication.^[21] However, as it has limited antitubercular activity, there was not full response. Immunocompromised state due to undergoing chemotherapy might have aggravated the disease to miliary stage in both the lungs
NHL coexisting with TBLN in the same node: It has been reported that TBLN usually are maximum of 4 cm in size, whereas NHL nodes can commonly become larger than that.^[22] Our case had LN of size ranging from 4.5 to 7.4 cm in cervical and axillary group, respectively, which is slightly bigger for it to be tubercular considering no prior history of TB or contact with TB patient
The patient acquired TB as a result of the immunocompromised state developed while undergoing chemotherapy. Further investigations confirmed the diagnosis of the same.

Summary

There is an increased risk of acquiring TB in cancer. Similarities in the presentation of NHL and TB can lead to misdiagnosis. Coexistence of lymphoma and TB is possible but less reported and can delay the definite diagnosis. TBLN masquerading cancer can upstage the disease leading to change in intent of treatment and management. Dissemination of TB as a result of immunosuppressive treatment used can be fatal. We should be careful in classifying LN without histological evidence specially those at unusual site or when unexpected disease response is observed. Even in LN with a histological proof of malignancy assessment for TB should be done.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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